新诊断的特发性颅内高压患者脑脊液和血浆中降钙素基因相关肽的前瞻性横断面病例对照研究
Calcitonin gene-related peptide in newly diagnosed idiopathic intracranial hypertension: a prospective, cross-sectional, case-control study of cerebrospinal fluid and plasma.
作者信息
Hansen Nadja Skadkær, Korsbaek Johanne Juhl, Bak Lasse Kristoffer, Jørgensen Niklas Rye, Beier Dagmar, Jensen Rigmor Højland
机构信息
Danish Headache Center, Department of Neurology, Rigshospitalet-Glostrup, University of Copenhagen, Copenhagen, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
出版信息
J Headache Pain. 2025 Apr 29;26(1):95. doi: 10.1186/s10194-025-02042-y.
BACKGROUND
Calcitonin Gene-Related Peptide (CGRP) is involved in migraine pain signaling, and blockage hereof is effective in migraine treatment. Headache in idiopathic intracranial hypertension (IIH) is often migraine-like but the underlying mechanisms are not understood. We report levels of CGRP in plasma and cerebrospinal fluid (CSF) of patients with newly diagnosed IIH to elucidate CGRP involvement in the pathogenesis of headache in IIH.
METHOD
We consecutively enrolled patients suspected of having IIH in a prospective cohort at two Danish tertiary headache centers. Patients are confirmed to have IIH or disproven of it (non-IIH). We included non-IIH with primary headache disorders as headache controls to IIH cases. We also recruited sex-, age- and BMI-matched healthy controls (HC). All participants had CSF and blood drawn and CGRP was analyzed using a validated radioimmunoassay. CSF plasma-ratios were calculated. Between-group levels were compared with ANOVA or Kruskal-Walli's test. In sub-analyses we restricted comparison of HC to non-IIH/IIH with chronic migraine; we also compared IIH with versus without headache. We correlated CGRP to lumbar opening pressure (OP), and BMI, and assessed the correlation between CGRP in plasma and CSF. Generalized or linear regression was applied to adjust for confounding by BMI, age, and active smoking.
RESULTS
Comparing 97 patients with IIH, 52 non-IIH, and 37 HC, we found no between-group differences in CGRP levels in plasma (p = 0.78), CSF (p = 0.79), or in CSF:plasma-ratio (p = 0.13). Adjusting for BMI, age, and smoking yielded similar results. CGRP levels were neither associated with having a migraine phenotype or chronic headache, nor with having any headache versus no headache in IIH. CGRP in plasma correlated with CGRP in CSF (p < 0.0001). CGRP did not correlate with OP or BMI.
CONCLUSION
CGRP levels in plasma and CSF and their ratios were comparable in IIH, non-IIH patients with headache, and sex-, age-, and BMI-matched HC. CGRP in plasma correlated with CGRP in CSF. Due to methodology, we probably measured basal resting CGRP. The role of CGRP in IIH-headache needs further clarification. A headache preventive effect in IIH of anti-CGRP targeted therapy remains a relevant unexplored area.
背景
降钙素基因相关肽（CGRP）参与偏头痛疼痛信号传导，阻断该信号传导对偏头痛治疗有效。特发性颅内高压（IIH）引起的头痛通常类似偏头痛，但潜在机制尚不清楚。我们报告新诊断的IIH患者血浆和脑脊液（CSF）中的CGRP水平，以阐明CGRP在IIH头痛发病机制中的作用。
方法
我们在丹麦的两个三级头痛中心的前瞻性队列中连续纳入疑似患有IIH的患者。患者被确诊为患有IIH或被排除（非IIH）。我们纳入患有原发性头痛疾病的非IIH患者作为IIH病例的头痛对照。我们还招募了性别、年龄和BMI匹配的健康对照（HC）。所有参与者均采集了脑脊液和血液，并使用经过验证的放射免疫分析法分析CGRP。计算脑脊液与血浆的比值。组间水平采用方差分析或Kruskal-Walli检验进行比较。在亚分析中，我们将HC与患有慢性偏头痛的非IIH/IIH患者进行比较；我们还比较了有头痛和无头痛的IIH患者。我们将CGRP与腰椎开口压力（OP）和BMI进行相关性分析，并评估血浆和脑脊液中CGRP之间的相关性。应用广义或线性回归来调整BMI、年龄和主动吸烟的混杂因素。
结果
比较97例IIH患者、52例非IIH患者和37例HC，我们发现血浆（p = 0.78）、脑脊液（p = 0.79）中的CGRP水平或脑脊液与血浆的比值（p = 0.13）在组间无差异。调整BMI、年龄和吸烟因素后结果相似。CGRP水平与偏头痛表型或慢性头痛无关，也与IIH患者有无头痛无关。血浆中的CGRP与脑脊液中的CGRP相关（p < 0.0001）。CGRP与OP或BMI无相关性。
结论
IIH患者、患有头痛的非IIH患者以及性别、年龄和BMI匹配的HC的血浆和脑脊液中的CGRP水平及其比值具有可比性。血浆中的CGRP与脑脊液中的CGRP相关。由于方法学原因，我们可能测量的是基础静息CGRP。CGRP在IIH头痛中的作用需要进一步阐明。抗CGRP靶向治疗对IIH头痛的预防作用仍是一个相关的未探索领域。
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